1.A phase Ⅲ follow-up study of recombinant human follicle-stimulating hormone (Follitrope ?) over 6.5 years
Zhiqin BU ; Linli HU ; Songying ZHANG ; Jieqiang LYU ; Song QUAN ; Yuanhua HUANG ; Weiping QIAN ; Yingpu SUN
Chinese Journal of Reproduction and Contraception 2024;44(12):1258-1264
Objective:To follow-up the previous phase Ⅲ clinical trial of recombinant human follicle-stimulating hormone (Follitrope ?), and to evaluate the cumulative pregnancy rate, the cumulative live birth rate, and the neonatal outcomes of subjects. Methods:The phase Ⅲ clinical study of Follitrope ? in China (CTR20150341/CTR20150341, May 15, 2015—June 27, 2016) was followed up until December 31, 2022. Patients were divided into Follitrope ? group and Gonal-F ? group. According to the age, patients were divided into three subgroups: 20-30 years old subgroup, 31-35 years old subgroup and 36-39 years old subgroup. Cumulative pregnancy rate, cumulative live birth rate, number of embryos transferred per cycle, live births per embryo transfer cycle, live births per oocyte retrieved, and neonatal characteristics were analyzed. Results:A total of 446 patients were included in the analysis, of which 336 (75.3%) were in the Follitrope ? group and 110 (24.7%) in the Gonal-F ? group, with a follow-up period of 6.5 years. There were no statistically significant differences between the Follitrope ? group and the Gonal-F ? group in terms of cumulative pregnancy rate and cumulative live birth rate (all P>0.05). Similar cumulative pregnancy rates and cumulative live birth rates were observed between the two groups within each age subgroup (all P>0.05). In the 36-39 years old subgroup, the Follitrope ? group showed a trend towards higher cumulative pregnancy rate [60.0% (12/20)] and cumulative live birth rate [55.0% (11/20)] compared with the Gonal-F ? group [28.6% (2/7), 14.3% (1/7)], however, none of the differences were statistically significant (all P>0.05). Twin pregnancy rates, live births per embryo, live birth per oocyte, newborn gender, birth weight, and birth defect rates were similar between the Follitrope ? group and the Gonal-F ? group without statistically significant differences (all P>0.05). Conclusion:The safety and effectiveness of Follitrope ? in controlled ovarian hyperstimulation are similar to those of Gonal-F ?. Compared with Gonal-F ?, there is a trend toward higher cumulative pregnancy rates and cumulative live birth rates in elderly patients with Follitrope ?, although there is no statistical difference.
2.A phase Ⅲ follow-up study of recombinant human follicle-stimulating hormone (Follitrope ?) over 6.5 years
Zhiqin BU ; Linli HU ; Songying ZHANG ; Jieqiang LYU ; Song QUAN ; Yuanhua HUANG ; Weiping QIAN ; Yingpu SUN
Chinese Journal of Reproduction and Contraception 2024;44(12):1258-1264
Objective:To follow-up the previous phase Ⅲ clinical trial of recombinant human follicle-stimulating hormone (Follitrope ?), and to evaluate the cumulative pregnancy rate, the cumulative live birth rate, and the neonatal outcomes of subjects. Methods:The phase Ⅲ clinical study of Follitrope ? in China (CTR20150341/CTR20150341, May 15, 2015—June 27, 2016) was followed up until December 31, 2022. Patients were divided into Follitrope ? group and Gonal-F ? group. According to the age, patients were divided into three subgroups: 20-30 years old subgroup, 31-35 years old subgroup and 36-39 years old subgroup. Cumulative pregnancy rate, cumulative live birth rate, number of embryos transferred per cycle, live births per embryo transfer cycle, live births per oocyte retrieved, and neonatal characteristics were analyzed. Results:A total of 446 patients were included in the analysis, of which 336 (75.3%) were in the Follitrope ? group and 110 (24.7%) in the Gonal-F ? group, with a follow-up period of 6.5 years. There were no statistically significant differences between the Follitrope ? group and the Gonal-F ? group in terms of cumulative pregnancy rate and cumulative live birth rate (all P>0.05). Similar cumulative pregnancy rates and cumulative live birth rates were observed between the two groups within each age subgroup (all P>0.05). In the 36-39 years old subgroup, the Follitrope ? group showed a trend towards higher cumulative pregnancy rate [60.0% (12/20)] and cumulative live birth rate [55.0% (11/20)] compared with the Gonal-F ? group [28.6% (2/7), 14.3% (1/7)], however, none of the differences were statistically significant (all P>0.05). Twin pregnancy rates, live births per embryo, live birth per oocyte, newborn gender, birth weight, and birth defect rates were similar between the Follitrope ? group and the Gonal-F ? group without statistically significant differences (all P>0.05). Conclusion:The safety and effectiveness of Follitrope ? in controlled ovarian hyperstimulation are similar to those of Gonal-F ?. Compared with Gonal-F ?, there is a trend toward higher cumulative pregnancy rates and cumulative live birth rates in elderly patients with Follitrope ?, although there is no statistical difference.
3.Identification and expression analysis of NHX gene family in Chinese cabbage.
Xuehua WANG ; Jia HAN ; Jizhong MA ; Xiting YANG ; Huali MAN ; Yali QIAO ; Xueqin GAO ; Linli HU
Chinese Journal of Biotechnology 2023;39(2):552-565
Na+/H+ antiporter (NHX) gene subfamily plays an important role in plant response to salt stress. In this study, we identified the NHX gene family members of Chinese cabbage and analyzed the expression patterns of BrNHXs gene in response to abiotic stresses such as high temperature, low temperature, drought and salt stress. The results showed that there were 9 members of the NHX gene family in Chinese cabbage, which were distributed on 6 chromosomes respectively. The number of amino acids was 513-1 154 aa, the relative molecular weight was 56 804.22-127 856.66 kDa, the isoelectric point was 5.35-7.68. Members of BrNHX gene family mainly existed in vacuoles, the gene structure is complete, and the number of exons is 11-22. The secondary structures of the proteins encoded by the NHX gene family in Chinese cabbage had alpha helix, beta turn and random coil, and the alpha helix occurred more frequently. Quantitative real-time PCR (qRT-PCR) analysis showed that the gene family members had different responses to high temperature, low temperature, drought and salt stress, and their expression levels differed significantly in different time periods. BrNHX02 and BrNHX09 had the most significant responses to these four stresses, and their expression levels were significantly up-regulated at 72 h after treatments, which could be used as candidate genes to further verify their functions.
Genome, Plant
;
Multigene Family
;
Stress, Physiological/genetics*
;
Brassica/metabolism*
;
Gene Expression Regulation, Plant
;
Phylogeny
;
Plant Proteins/metabolism*
4.Effect of inactive tuberculosis on pregnancy outcome of IVF/ICSI-ET in infertile patients
Qi LI ; Zhiqin BU ; Ziyao YANG ; Linli HU
Chinese Journal of Reproduction and Contraception 2023;43(8):784-791
Objective:To explore the effect of inactive tuberculosis on the assisted reproductive outcome of the first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) in infertile patients. Methods:A retrospective cohort study was conducted to analyze the data of 15 412 infertile patients who underwent the first fresh-cycle embryo transfer in the Reproductive and Genetics Hospital of the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2021. They were divided into inactive tuberculosis group (635 cases) and control group (1 270 cases) according to the ratio of 1∶2 by propensity score matching (PSM). The inactive tuberculosis group was divided into three subgroups: tuberculosis (group A, 378 cases), pelvic tuberculosis (group B, 214 cases) and other tuberculosis (group C, 43 cases) according to the location. The inactive tuberculosis group was also divided into the treatment subgroup (377 cases) and the non-treatment subgroup (258 cases) according to whether they had undergone treatment. The assisted reproductive outcomes were compared and the influencing factors were analyzed.Results:After PSM, the difference of the baseline data between the inactive tuberculosis group and control group was not statistically significant (all P>0.05). The fertilization rate [65.2% (5 207/7 991)] of patients in the inactive tuberculosis group was significantly higher than that of control group [63.7% (9 889/15 524), P=0.027], but the implantation rate [41.9% (483/1 152)], the clinical pregnancy rate [58.4% (371/635) ] and the live birth rate [46.5% (295/635)] were significantly lower than those of control group [48.8% (1 112/2 279), P<0.001; 67.2% (853/1 270), P<0.001; 57.9% (735/1 270), P<0.001], and the miscarriage rate [20.5% (76/371)] was significantly higher than that of control group [13.8% (118/853), P=0.003], and the endometrium thickness [(11.8±2.6) mm] was thinner than that of control group [(12.5±3.9) mm, P<0.001]. For subgroup analysis, the high-quality embryo rate in group B [62.3% (1 111/1 784)] was significantly lower than that in group A [66.5% (2 027/3 048), P=0.007] and control group [65.9% (6 516/9 889), P=0.007], and the difference was statistically significant. The implantation rate [46.6% (318/682)], the clinical pregnancy rate [64.5% (243/377)] and the live birth rate [51.7% (195/377)] in the treatment group were higher than those in the non-treatment group [35.1% (165/470), P<0.001;49.6% (128/258), P<0.001;38.8% (100/258), P=0.001]. In addition, logistic regression showed that inactive tuberculosis was an independent risk factor for clinical pregnancy, live birth, and miscarriage ( OR=0.71, 95% CI: 0.58-0.87, P=0.002; OR=0.65, 95% CI: 0.54-0.80, P<0.001; OR=1.58, 95% CI: 1.15-2.19, P=0.045). Conclusion:Inactive tuberculosis is an independent risk factor for adverse assisted reproductive outcomes. Compared with non-tuberculosis infertile patients, the pregnancy outcomes of inactive tuberculosis infertile patients who received IVF/ICSI-ET for the first time are poorer, especially the patients with pelvic tuberculosis in the past. Regular anti-tuberculosis treatment for tuberculosis patients can help to improve pregnancy outcomes.
5.Effect of inactive tuberculosis on pregnancy outcome of IVF/ICSI-ET in infertile patients
Qi LI ; Zhiqin BU ; Ziyao YANG ; Linli HU
Chinese Journal of Reproduction and Contraception 2023;43(8):784-791
Objective:To explore the effect of inactive tuberculosis on the assisted reproductive outcome of the first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) in infertile patients. Methods:A retrospective cohort study was conducted to analyze the data of 15 412 infertile patients who underwent the first fresh-cycle embryo transfer in the Reproductive and Genetics Hospital of the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2021. They were divided into inactive tuberculosis group (635 cases) and control group (1 270 cases) according to the ratio of 1∶2 by propensity score matching (PSM). The inactive tuberculosis group was divided into three subgroups: tuberculosis (group A, 378 cases), pelvic tuberculosis (group B, 214 cases) and other tuberculosis (group C, 43 cases) according to the location. The inactive tuberculosis group was also divided into the treatment subgroup (377 cases) and the non-treatment subgroup (258 cases) according to whether they had undergone treatment. The assisted reproductive outcomes were compared and the influencing factors were analyzed.Results:After PSM, the difference of the baseline data between the inactive tuberculosis group and control group was not statistically significant (all P>0.05). The fertilization rate [65.2% (5 207/7 991)] of patients in the inactive tuberculosis group was significantly higher than that of control group [63.7% (9 889/15 524), P=0.027], but the implantation rate [41.9% (483/1 152)], the clinical pregnancy rate [58.4% (371/635) ] and the live birth rate [46.5% (295/635)] were significantly lower than those of control group [48.8% (1 112/2 279), P<0.001; 67.2% (853/1 270), P<0.001; 57.9% (735/1 270), P<0.001], and the miscarriage rate [20.5% (76/371)] was significantly higher than that of control group [13.8% (118/853), P=0.003], and the endometrium thickness [(11.8±2.6) mm] was thinner than that of control group [(12.5±3.9) mm, P<0.001]. For subgroup analysis, the high-quality embryo rate in group B [62.3% (1 111/1 784)] was significantly lower than that in group A [66.5% (2 027/3 048), P=0.007] and control group [65.9% (6 516/9 889), P=0.007], and the difference was statistically significant. The implantation rate [46.6% (318/682)], the clinical pregnancy rate [64.5% (243/377)] and the live birth rate [51.7% (195/377)] in the treatment group were higher than those in the non-treatment group [35.1% (165/470), P<0.001;49.6% (128/258), P<0.001;38.8% (100/258), P=0.001]. In addition, logistic regression showed that inactive tuberculosis was an independent risk factor for clinical pregnancy, live birth, and miscarriage ( OR=0.71, 95% CI: 0.58-0.87, P=0.002; OR=0.65, 95% CI: 0.54-0.80, P<0.001; OR=1.58, 95% CI: 1.15-2.19, P=0.045). Conclusion:Inactive tuberculosis is an independent risk factor for adverse assisted reproductive outcomes. Compared with non-tuberculosis infertile patients, the pregnancy outcomes of inactive tuberculosis infertile patients who received IVF/ICSI-ET for the first time are poorer, especially the patients with pelvic tuberculosis in the past. Regular anti-tuberculosis treatment for tuberculosis patients can help to improve pregnancy outcomes.
6.Study on reducing perineal incision rate based on restrictive perineal incision evaluation tool combined with prone flexion delivery
Chengfen YANG ; Li QIAN ; Lingping XUAN ; Xian LU ; Wei HUANG ; Linli HU
Chinese Journal of Modern Nursing 2022;28(33):4686-4691
Objective:To explore the effect of restrictive perineal incision evaluation combined with prone flexion delivery on reducing the perineal incision rate.Methods:The convenient sampling method was used to select 440 primiparas who delivered naturally in Wuxi People's Hospital Affiliated to Nanjing Medical University from June to November 2020 as research objects. According to the random number table method, the primiparas were divided into the observation group and the control group, with 220 cases in each group. The observation group was scored item by item according to the Restrictive Perineotomy Assessment Scale, and the indications of perineotomy were strictly performed according to the final score. The control group judged whether to undergo perineotomy according to subjective experience. The prone flexion delivery was used in both groups and the delivery outcomes of the two groups were compared.Results:The perineal incision rate of the observation group was lower than that of the control group, and the difference was statistically significant ( P<0.01) . The perineal laceration degree of the observation group was less than that of the control group, and the difference was statistically significant ( P< 0.05) . The rate of poor perineal wound healing in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . The degree of postpartum perineal pain in the observation group was less than that in the control group, and the difference was statistically significant ( P<0.01) . There was no statistically significant difference in the incidence of neonatal asphyxia between the two groups ( P>0.05) . There was no neonatal injury in the two groups. Conclusions:Construction and application of Restrictive Perineotomy Assessment Scale avoid midwives to judge based on subjective experience and improve the accuracy of perineotomy assessment. The combination with prone flexion delivery can further reduce the rate of perineotomy and poor healing rate of postpartum perineal wound and reduce postpartum perineal pain, which is an effective method to improve postpartum perineal outcome and ensure the safety of mother and children.
7.Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles
Yimin ZHU ; Yue GAO ; Donghong NAI ; Linli HU ; Lei JIN ; Ying ZHONG ; Ze WU ; Guimin HAO ; Qiongfang WU ; Yichun GUAN ; Hong JIANG ; Cuilian ZHANG ; Minli LIU ; Xiaohong WANG ; Xiaoming TENG ; Jinliang DUAN ; Liran LI ; Yue ZHANG ; Hong YE
Chinese Journal of Obstetrics and Gynecology 2022;57(7):510-518
Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.
8.Influence of female age on the fresh cycle live birth rate of different controlled ovarian hyperstimulation protocols in poor ovarian response patients
Fei LI ; Tian YE ; Huijuan KONG ; Jing LI ; Linli HU ; Hongyi YANG ; Yihong GUO ; Gang LI
Chinese Journal of Obstetrics and Gynecology 2021;56(7):482-488
Objective:To investigate the influence of age on the fresh cycle live birth rate in patients with poor ovarian response in different controlled ovarian hyperstimulation groups.Methods:The clinical data of 3 342 patients in The First Affiliated Hospital of Zhengzhou University from February 2014 to November 2018 were retrospectively collected, including early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol group (1 375 cases), mid-luteal phase short-acting GnRH agonist long protocol group (1 161 cases) and GnRH antagonist protocol group (806 cases); each group was divided into 4 subgroups according to age: ≤30 years, 31-35 years, 36-40 years and >40 years, the pregnancy outcomes in each age subgroup were analyzed under different controlled ovarian hyperstimulation protocols.Results:In early-follicular phase long-acting GnRH agonist long protocol group, the final live birth rates of each age subgroup were 39.4% (228/579), 36.1% (135/374), 16.6% (48/290) and 3.0% (4/132); in mid-luteal phase short-acting GnRH agonist long protocol group, live birth rates of each age subgroup were 32.1% (99/308), 20.8% (55/264), 13.0% (45/346) and 7.0% (17/243); in GnRH antagonist protocol group, live birth rates of each age subgroup were 22.8% (26/114), 16.3% (25/153), 11.2% (31/278), and 3.8% (10/261); the live birth rate of each group decreased significantly with the increase of age (all P<0.01). When the age≤35 years old, the fresh cycle live birth rate of the early-follicular phase long-acting GnRH agonist long protocol group was significantly better than those of the other two groups (all P<0.01). The multivariate logistic regression analysis of age and live birth rate of the three controlled ovarian hyperstimulation groups showed age was the independent influence factor ( OR=0.898, 95% CI: 0.873-0.916, P<0.01; OR=0.926, 95% CI: 0.890-0.996, P<0.01; OR=0.901, 95% CI: 0.863-0.960, P<0.01). Conclusions:Age is an independent influencing factor for the prediction of fresh cycle live birth rate in low ovarian response patients. No matter which controlled ovarian hyperstimulation protocol is adopted, the final live birth rate decreases significantly with the increase of women′s age. In addition, the early-follicular phase long-acting GnRH agonist long protocol has the highest fresh cycle live birth rate among all controlled ovarian hyperstimulation groups.
9.Optimum number of oocytes retrieved of follicular phase long-acting long protocol in patients with high ovarian reverse
Chinese Journal of Reproduction and Contraception 2020;40(4):265-270
Objective:To observe the clinical characteristics and the optimum number of oocytes retrieved of follicular phase long-acting long protocol in patient with high ovarian reverse.Methods:A total of 5168 patients with polycystic ovary/polycystic ovary syndrome (PCO/PCOS) underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University from August 2015 to July 2019 were retrospectively identified. The cycles were divided into two groups according if “freeze all embryos” for high ovarian response, divided into groups according to whether the patients underwent moderate to severe ovarian hyperstimulation syndrome (OHSS) after embryo transfer, and divided into six groups for the number of oocytes retrieved: <6, 6-10, 11-15, 16-20, 21-25, ≥26. Clinical characteristics, clinical pregnancy rate, freeze-all rate for high response and moderate to severe OHSS rate after embryo transfer in different groups were compared. Logistic regression analysis was used to analyze the correlation of the number of oocytes retrieved to high ovarian response and the moderate or severe OHSS occurence after embryo transfer. Results:In IVF cycles stimulated with follicular phase long-acting long protocol, the optimal number of oocytes for achieving clinical pregnancy was 6-10, 11-15, 16-20 (72.05%, 74.29%, 76.17%), and also had a lower chance of all embryo frozen rate (2.46%, 10.01%, 23.59%). The number of oocytes retrieved was associated with embryo frozen rate ( OR=2.159, 95% CI=2.027-2.300, P<0.001), and not associated with moderate to severe OHSS after embryo transfer ( OR=0.755, 95% CI=0.553-1.031, P=0.077). Conclusion:The optimal number of oocytes for PCO/PCOS patient stimulated with follicular phase long-acting long protocol is between 6 and 20.
10.Optimum number of oocytes retrieved of follicular phase long-acting long protocol in patients with high ovarian reverse
Chinese Journal of Reproduction and Contraception 2020;40(4):265-270
Objective:To observe the clinical characteristics and the optimum number of oocytes retrieved of follicular phase long-acting long protocol in patient with high ovarian reverse.Methods:A total of 5168 patients with polycystic ovary/polycystic ovary syndrome (PCO/PCOS) underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University from August 2015 to July 2019 were retrospectively identified. The cycles were divided into two groups according if “freeze all embryos” for high ovarian response, divided into groups according to whether the patients underwent moderate to severe ovarian hyperstimulation syndrome (OHSS) after embryo transfer, and divided into six groups for the number of oocytes retrieved: <6, 6-10, 11-15, 16-20, 21-25, ≥26. Clinical characteristics, clinical pregnancy rate, freeze-all rate for high response and moderate to severe OHSS rate after embryo transfer in different groups were compared. Logistic regression analysis was used to analyze the correlation of the number of oocytes retrieved to high ovarian response and the moderate or severe OHSS occurence after embryo transfer. Results:In IVF cycles stimulated with follicular phase long-acting long protocol, the optimal number of oocytes for achieving clinical pregnancy was 6-10, 11-15, 16-20 (72.05%, 74.29%, 76.17%), and also had a lower chance of all embryo frozen rate (2.46%, 10.01%, 23.59%). The number of oocytes retrieved was associated with embryo frozen rate ( OR=2.159, 95% CI=2.027-2.300, P<0.001), and not associated with moderate to severe OHSS after embryo transfer ( OR=0.755, 95% CI=0.553-1.031, P=0.077). Conclusion:The optimal number of oocytes for PCO/PCOS patient stimulated with follicular phase long-acting long protocol is between 6 and 20.

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